Hepatitis B virus RNA and hepatitis B surface antigen kinetics predict treatment outcomes in children with chronic hepatitis B

TL;DR

This study shows that measuring specific virus markers early in treatment helps predict outcomes in children with hepatitis B, especially when combined with age.

Contribution

The study introduces pgRNA and HBsAg kinetics as early predictors of treatment outcomes in children with chronic hepatitis B.

Findings

Early pgRNA decline predicts HBeAg seroconversion better than DNA or HBsAg levels.

Combining HBsAg decline with patient age improves prediction of HBsAg loss.

Younger children (under 7) have better treatment outcomes than older children.

Abstract

Serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) predicts antiviral response in adults with chronic hepatitis B (CHB); however, its prognostic performance against conventional biomarkers in children remains underexplored. This study aimed to characterize the kinetics of pgRNA and hepatitis B surface antigen (HBsAg) and evaluate their predictive value for treatment outcomes in children with CHB.

Sixty-five hepatitis B e antigen (HBeAg)-positive children with CHB who received ≥ 96 weeks of nucleos(t)ide analogue (NA) therapy were included. Serum viral biomarkers were measured at baseline, weeks 12, 48, and 96. Treatment outcomes were HBeAg seroconversion and HBsAg loss (Defined as HBsAg <100 IU/mL or seroclearance).

Patients initiating treatment before age 7 years had a significantly higher cumulative incidence of HBeAg seroconversion (73.5% vs. 48.4%) and HBsAg loss (50.0% vs. 9.7%) compared to older children (p < 0.05). Week 12 HBV pgRNA decline was an independent predictor of HBeAg seroconversion (area under the curve [AUC] = 0.793, 95% confidence interval [CI]: 0.686–0.900), outperforming HBV DNA and HBsAg kinetics. For predicting HBsAg loss, the week 12 HBsAg decline was an independent predictor (AUC = 0.762, 95% CI: 0.632–0.893), and its integration with patient age further improved predictive accuracy (AUC = 0.879, 95% CI: 0.796–0.962).

Early pgRNA kinetics more accurately predict HBeAg seroconversion, whereas HBsAg dynamics forecast HBsAg loss more effectively, particularly when combined with patient age. This complementary monitoring strategy provides a clinically applicable tool for optimizing personalized management in children with CHB.

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